Role Of CB1 Cannabinoid Receptor Research Articles

Role of CB1 Cannabinoid Receptors in Vascular Responses and Vascular Remodeling of the Aorta in Female Mice.

Both the endocannabinoid system (ECS) and estrogens have significant roles in cardiovascular control processes. Cannabinoid type 1 receptors (CB1Rs) mediate acute vasodilator and hypotensive effects, although their role in cardiovascular pathological conditions is still controversial. Estrogens exert cardiovascular protection in females. We aimed to study the impact of ECS on vascular functions. Experiments were performed on CB1R knockout (CB1R KO) and wild-type (WT) female mice. Plasma estrogen metabolite levels were determined. Abdominal aortas were isolated for myography and histology. Vascular effects of phenylephrine (Phe), angiotensin II, acetylcholine (Ach) and estradiol (E2) were obtained and repeated with inhibitors of nitric oxide synthase (NOS, Nω-nitro-L-arginine) and of cyclooxygenase (COX, indomethacin). Histological stainings (hematoxylin-eosin, resorcin-fuchsin) and immunostainings for endothelial NOS (eNOS), COX-2, estrogen receptors (ER-α, ER-β) were performed. Conjugated E2 levels were higher in CB1R KO compared to WT mice. Vasorelaxation responses to Ach and E2 were increased in CB1R KO mice, attenuated by NOS-inhibition. COX-inhibition decreased Phe-contractions, while it increased Ach-relaxation in the WT group but not in the CB1R KO. Effects of indomethacin on E2-relaxation in CB1R KO became opposite to that observed in WT. Histology revealed lower intima/media thickness and COX-2 density, higher eNOS and lower ER-β density in CB1R KO than in WT mice. CB1R KO female mice are characterized by increased vasorelaxation associated with increased utilization of endothelial NO and a decreased impact of constrictor prostanoids. Our results indicate that the absence or inhibition of CB1Rs may have beneficial vascular effects.

CB1 Cannabinoid Receptors Mediate Cognitive Deficits and Structural Plasticity Changes During Nicotine Withdrawal

BackgroundTobacco withdrawal is associated with deficits in cognitive function, including attention, working memory, and episodic memory. Understanding the neurobiological mechanisms involved in these effects is crucial because cognitive deficits during nicotine withdrawal may predict relapse in humans. MethodsWe investigated in mice the role of CB1 cannabinoid receptors (CB1Rs) in memory impairment and spine density changes induced by nicotine withdrawal precipitated by the nicotinic antagonist mecamylamine. Drugs acting on the endocannabinoid system and genetically modified mice were used. ResultsMemory impairment during nicotine withdrawal was blocked by the CB1R antagonist rimonabant or the genetic deletion of CB1R in forebrain gamma-aminobutyric acidergic (GABAergic) neurons (GABA-CB1R). An increase of 2-arachidonoylglycerol (2-AG), but not anandamide, was observed during nicotine withdrawal. The selective inhibitor of 2-AG biosynthesis O7460 abolished cognitive deficits of nicotine abstinence, whereas the inhibitor of 2-AG enzymatic degradation JZL184 did not produce any effect in cognitive impairment. Moreover, memory impairment was prevented by the selective mammalian target of rapamycin inhibitor temsirolimus and the protein synthesis inhibitor anisomycin. Mature dendritic spines on CA1 pyramidal hippocampal neurons decreased 4 days after the precipitation of nicotine withdrawal, when the cognitive deficits were still present. Indeed, a correlation between memory performance and mature spine density was found. Interestingly, these structural plasticity alterations were normalized in GABA-CB1R conditional knockout mice and after subchronic treatment with rimonabant. ConclusionsThese findings underline the interest of CB1R as a target to improve cognitive performance during early nicotine withdrawal. Cognitive deficits in early abstinence are associated with increased relapse risk.

Dissociation between the panicolytic effect of cannabidiol microinjected into the substantia nigra, pars reticulata, and fear-induced antinociception elicited by bicuculline administration in deep layers of the superior colliculus: The role of CB1-cannabinoid receptor in the ventral mesencephalon

Many studies suggest that the substantia nigra, pars reticulata (SNpr), a tegmental mesencephalic structure rich in γ-aminobutyric acid (GABA)- and cannabinoid receptor-containing neurons, is involved in the complex control of defensive responses through the neostriatum-nigral disinhibitory and nigro-tectal inhibitory GABAergic pathways during imminently dangerous situations. The aim of the present work was to investigate the role played by CB1-cannabinoid receptor of GABAergic pathways terminal boutons in the SNpr or of SNpr-endocannabinoid receptor-containing interneurons on the effect of intra-nigral microinjections of cannabidiol in the activity of nigro-tectal inhibitory pathways. GABAA receptor blockade in the deep layers of the superior colliculus (dlSC) elicited vigorous defensive behaviour. This explosive escape behaviour was followed by significant antinociception. Cannabidiol microinjection into the SNpr had a clear anti-aversive effect, decreasing the duration of defensive alertness, the frequency and duration of defensive immobility, and the frequency and duration of explosive escape behaviour, expressed by running and jumps, elicited by transitory GABAergic dysfunction in dlSC. However, the innate fear induced-antinociception was not significantly changed. The blockade of CB1 endocannabinoid receptor in the SNpr decreased the anti-aversive effect of canabidiol based on the frequency and duration of defensive immobility, the frequency of escape expressed by running, and both the frequency and duration of escape expressed by jumps. These findings suggest a CB1 mediated endocannabinoid signalling in cannabidiol modulation of panic-like defensive behaviour, but not of innate fear-induced antinociception evoked by GABAA receptor blockade with bicuculline microinjection into the superior colliculus, with a putative activity in nigro-collicular GABAergic pathways.

The endocannabinoid system: a key modulator of emotions and cognition

The endocannabinoid system: a key modulator of emotions and cognition

Role of CB1 cannabinoid receptor in the modulation of pituitary hormone secretion

Event Abstract Back to Event Role of CB1 cannabinoid receptor in the modulation of pituitary hormone secretion Ibolya Bodnár1, Márk Oláh1*, Dániel Hechtl1, Tibor Wenger2, Miklós Góth3, Valéria Rettoni4 and György M. Nagy1 1 Neuromorphological and Neuroendocrine Research Laboratory, Hungarian Academy of Sciences–Semmelweis University, Department of Human Morphology and Developmental Biology, Hungary 2 Semmelweis University, Department of Human Morphology and Developmental Biology, Hungary 3 State Health Centre, Division of Internal Medicine, Hungary 4 CONICET, Universidad de Buenos Aires, Facultad de Medicina, Centro de Estudios Farmacológicos y Botánicos, Argentina Background and Aims: It is known that cannabinoids can modulate anterior pituitary hormone secretion through a supposed crosstalk between CB1 receptor (CB1R) and different G-protein coupled receptors (GPCRs). We have investigated the significance of CB1 receptor in dopamine- (DA) and angiotensin II (AII) induced prolactin (PRL) and adrenocorticotroph hormone (ACTH) release as well as ghrelin- and growth hormone-releasing hormone (GHRH) induced growth hormone (GH) release using pituitary cell cultures derived from wild type (WT) and CB1 knock-out (CB1KO) mice. Dispersed anterior lobe cells were used immediately after dispersion in the PRL reverse hemolytic plaque assay (RHPA) and/or following 24 hours culture, then the concentration of PRL, ACTH and GH of the culture media was measured by specific RIA. Cells were treated with DA or TRH and with angiotensin II (AII), AM251 (CB1 antagonist), ghrelin or GHRH in the RHPA and in primary cultures, respectively. Results: DA exhibited similar inhibition on PRL release in both WT and CB1KO animals however the number of PRL cells were almost doubled in CB1KO mice detected in the RHPA. AII could strongly stimulate PRL and ACTH secretion in WT animals, while in the CB1KO group PRL release was absent and ACTH release was enhanced. Pretreatment of cultured cells with AM251 prevented AII induced PRL but not ACTH response in WT mice. Basal release of GH was significantly higher in CB1KO mice but the stimulating effects of ghrelin and GHRH were the same in both groups. Conclusion: Our results clearly show that the lack of CB1R profoundly affects secretagogues induced pituitary hormone release in vitro, therefore, indicates an intra-pituitary role of the endocannabinoid system in hormone release. This work was supported by the OTKA-68170 and 68660, ETT-458/09 and Hungarian–Argentinean Intergovermental S&T Cooperation Programme ARG 20/2006. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Homeostatic and neuroendocrine systems Citation: Bodnár I, Oláh M, Hechtl D, Wenger T, Góth M, Rettoni V and Nagy GM (2010). Role of CB1 cannabinoid receptor in the modulation of pituitary hormone secretion. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00110 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Apr 2010; Published Online: 23 Apr 2010. * Correspondence: Márk Oláh, Neuromorphological and Neuroendocrine Research Laboratory, Hungarian Academy of Sciences–Semmelweis University, Department of Human Morphology and Developmental Biology, Budapest, Hungary, olahmark@ana2.sote.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ibolya Bodnár Márk Oláh Dániel Hechtl Tibor Wenger Miklós Góth Valéria Rettoni György M Nagy Google Ibolya Bodnár Márk Oláh Dániel Hechtl Tibor Wenger Miklós Góth Valéria Rettoni György M Nagy Google Scholar Ibolya Bodnár Márk Oláh Dániel Hechtl Tibor Wenger Miklós Góth Valéria Rettoni György M Nagy PubMed Ibolya Bodnár Márk Oláh Dániel Hechtl Tibor Wenger Miklós Góth Valéria Rettoni György M Nagy Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Effects of the cannabinoid CB1 receptor antagonist AM 251 on the reinstatement of nicotine-conditioned place preference by drug priming in rats

Tobacco and cannabis are among the most widely abused drugs in humans, and recently, the functional interaction between nicotine and cannabinoids has been reported. The aim of the present studies is to evaluate the role of CB1 cannabinoid receptors in the reinstatement of nicotine-induced conditioned place preference. Nicotine-induced conditioned place preference was established (threeday nicotine sessions, 0.5mg/kg), extinguished and reinstated by a priming dose of nicotine. It was shown that the CB1 receptor antagonist AM 251 (0.25 and 0.5mg/kg) in a dose-dependent manner attenuates the reinstatement of nicotine place conditioning. These studies suggest a role for CB1 cannabinoids receptors in preventing the reinstatement of nicotine addiction.

Lack of CB1 Cannabinoid Receptor Impairs Cocaine Self-Administration

Acute rewarding properties are essential for the establishment of cocaine addiction, and multiple neurochemical processes participate in this complex behavior. In the present study, we used the self-administration paradigm to evaluate the role of CB1 cannabinoid receptors in several aspects of cocaine reward, including acquisition, maintenance, and motivation to seek the drug. For this purpose, both CB1 receptor knockout mice and wild-type littermates were trained to intravenously self-administer cocaine under different schedules. Several cocaine training doses (0.32, 1, and 3.2 mg/kg/infusion) were used in the acquisition studies. Only 25% of CB1 knockout mice vs 75% of their wild-type littermates acquired a reliable operant responding to self-administer the most effective dose of cocaine (1 mg/kg/infusion), and the number of sessions required to attain this behavior was increased in knockout mice. Animals reaching the acquisition criteria were evaluated for the motivational strength of cocaine as a reinforcer under a progressive ratio schedule. The maximal effort to obtain a cocaine infusion was significantly reduced after the genetic ablation of CB1 receptors. A similar result was obtained after the pharmacological blockade of CB1 receptors with SR141716A in wild-type mice. Moreover, the cocaine dose-response curve was flattened in the knockout group, suggesting that the differences observed between genotypes were related to changes in the reinforcing efficacy of the training dose of cocaine. Self-administration for water and food was not altered in CB1 knockout mice in any of the reinforcement schedules used, which emphasizes the selective impairment of drug reinforcement in these knockout mice. Finally, cocaine effects on mesolimbic dopaminergic transmission were evaluated by in vivo microdialysis in these mice. Acute cocaine administration induced a similar enhancement in the extracellular levels of dopamine in the nucleus accumbens of both CB1 knockout and wild-type mice. This work clearly demonstrates that CB1 receptors play an important role in the consolidation of cocaine reinforcement, although are not required for its acute effects on mesolimbic dopaminergic transmission.

Lack of CB1 cannabinoid receptors modifies nicotine behavioural responses, but not nicotine abstinence

Cannabis is the most widely consumed illicit drug and its consumption is currently associated with tobacco, which contains another psychoactive compound, namely nicotine. Interactions between cannabinoids and other drugs of abuse, such as opioids, have been previously reported. The aim of the present study was to evaluate the possible role of CB1 cannabinoid receptor in responses induced by acute and repeated nicotine administration by using knockout mice lacking the CB1 cannabinoid receptor and their wild-type littermates. Acute nicotine (0.5, 1, 3 and 6 mg/kg, sc) administration decreased locomotor activity and induced antinociceptive responses in the tail-immersion and the hot-plate test, in wild-type animals. The antinociceptive effects in the tail-immersion test were significantly enhanced in CB1 knockout mice. In wild-type mice nicotine (0.5 mg/kg, sc) produced a significant rewarding effect, as measured by a conditioned place preference paradigm. This response was absent in CB1 knockout mice. Finally, a model of mecamylamine-induced abstinence in chronic nicotine-treated mice (10 mg/kg/day, sc) was developed. Mecamylamine (1 and 2 mg/kg, sc) precipitated several somatic signs of nicotine withdrawal in wild-type dependent mice. However, no difference in the severity of nicotine withdrawal was observed in CB1 knockout mice. These results demonstrate that some acute effects and motivational responses elicited by nicotine can be modulated by the endogenous cannabinoid system and support the existence of a physiological interaction between these two systems.